From bench to bedside: targeting ferroptosis and mitochondrial damage in the treatment of diabetic cardiomyopathy DOI Creative Commons
Bin Liu, Qing Jin, Yi Sun

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Diabetic cardiomyopathy (DCM) is a common and fatal cardiac complication caused by diabetes, with its pathogenesis involving various forms of cell death mitochondrial dysfunction, particularly ferroptosis injury. Recent studies have indicated that damage play crucial roles in the onset progression DCM, though their precise regulatory mechanisms remain unclear. Of particular interest interaction between damage, as well synergistic effects, which are not fully understood. This review summarizes injury DCM explores molecular involved, an emphasis on interplay these two processes. Additionally, article offers overview targeted drugs shown to be effective cellular experiments, animal models, clinical trials, analyzing action potential side effects. The goal provide insights for future drug development applications. Moreover, challenges prospects multi-target combination therapies personalized medicine interventions practice offer strategic guidance comprehensive prevention management DCM.

Language: Английский

Dual‐Release Free Iron and Breakdown of Ferroptosis Defenses to Achieve Ferroptosis Cascade Storms for Potent Antitumor Therapy DOI Open Access

Wenting Xu,

Yuzhen Yang, Lijuan Liu

et al.

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract Ferroptosis is a newly identified type of regulated cell death characterized by iron‐dependent lipid peroxidation. Among the main ferroptosis‐suppressing systems, dihydroorotate dehydrogenase (DHODH)‐ ubiquinone axis closely related to mitochondria and energy metabolism, implying that protects cells from oxidative stress damage via maintenance redox homeostasis. However, ferroptosis initiation requires suitable environment breakthrough in homeostatic limitations systems. Hence, nanoparticles are rationally engineered achieve efficient induction releasing dual‐release free iron disrupting Atovaquone (ATO)‐loaded hollow mesoporous etching zeolitic imidazolate framework‐67 double‐coated oxide/calcium phosphate (Fe 3 O 4 /CaP) conjugated with polyethylene glycol. The external Fe /CaP structure enhances efficiency multiple reactive oxygen species (ROS) generation promoting stress. Still, it achieves increase content unstable pools for igniting ROS storm peroxidation spark. release ATO not only affects metabolism mitochondrial respiratory chain binding complex III but also downregulates DHODH restrict ubiquinol system disrupt Therefore, design this composite nanomedicine provides an approach inducing theoretical basis clinical anti‐tumor trials.

Language: Английский

Citations

1
Mitochondrial Dysfunction‐Evoked DHODH Acetylation is Involved in Renal Cell Ferroptosis during Cisplatin‐Induced Acute Kidney Injury DOI Creative Commons

Nannan Liang,

Yue‐Yue Guo,

Xiaoyi Zhang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(43)

Published: Sept. 20, 2024

Several studies have observed renal cell ferroptosis during cisplatin-induced acute kidney injury (AKI). However, the mechanism is not completely clear. In this study, oxidized arachidonic acid (AA) metabolites are increased in cisplatin-treated HK-2 cells. Targeted metabolomics showed that end product of pyrimidine biosynthesis decreased and initiating substrate mouse kidneys. Mitochondrial DHODH, a key enzyme for synthesis, its downstream CoQH2, downregulated. DHODH overexpression attenuated but silence exacerbated CoQH2 depletion lipid peroxidation. Mechanistically, acetylation elevated cisplatin-exposed mice. SIRT3 reduced kidneys Both vitro vivo NMN supplementation mitochondrial ferroptosis. By contrast, Sirt3 knockout aggravated ferroptosis, which can be by NMN. Additional experiments cisplatin caused dysfunction SUMOylation. Pretreatment with mitochondria-target antioxidant MitoQ alleviated cisplatin-caused dysfunction, SUMOylation, acetylation. pretreatment protected against AKI Taken together, these results suggest dysfunction-evoked partially contributes to AKI.

Language: Английский

Citations

4
5β-hydroxycostic acid from Laggera alata ameliorates sepsis-associated acute kidney injury through its anti-inflammatory and anti-ferroptosis effects via NF-κB and MAPK pathways DOI
Qing Li,

Xue Shi,

Hong Huang

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119359 - 119359

Published: Jan. 1, 2025

Language: Английский

Citations

0
Protein‐Interference‐Free and Kidney‐Targeting NIR Fluorophores for Accurate in Vivo Imaging of H2S2 during Kidney Ferroptosis DOI Open Access

Zhangkang Lv,

Jing Wang,

Jinyuan Xu

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

High-fidelity kidney function imaging is important for assessing the nephrotoxicity of drugs and diagnosing renal diseases. However, current challenges in achieving accurate include unspecific signal enhancement due to albumin binding relatively low distribution agents kidneys. Here, first time, a side-chain engineering strategy that incorporates hydrophilic six-membered heterocycles into aza-hemicyanine generating high-performance with protein-interference-free kidney-targeting features proposed. Based on these unique dyes, albumin-insensitive H2S2 near-infrared (NIR) fluorescent probe NA-H2S2 designed, which demonstrates effective following intravenous injection specifically activated by H2S2. The designed presents highly rapid, selective sensitive response detection limit as 24.21 nm. Additionally, it successfully achieves real-time vivo NIR fluorescence during erastin/cisplatin induced ferroptosis. Moreover, also enables rapid through vitro optical urinalysis, offering significant diagnostic value Overall, this study not only practical increased accuracy but provides promising dyes further development disease-related probes.

Language: Английский

Citations

0
From bench to bedside: targeting ferroptosis and mitochondrial damage in the treatment of diabetic cardiomyopathy DOI Creative Commons
Bin Liu, Qing Jin, Yi Sun

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Diabetic cardiomyopathy (DCM) is a common and fatal cardiac complication caused by diabetes, with its pathogenesis involving various forms of cell death mitochondrial dysfunction, particularly ferroptosis injury. Recent studies have indicated that damage play crucial roles in the onset progression DCM, though their precise regulatory mechanisms remain unclear. Of particular interest interaction between damage, as well synergistic effects, which are not fully understood. This review summarizes injury DCM explores molecular involved, an emphasis on interplay these two processes. Additionally, article offers overview targeted drugs shown to be effective cellular experiments, animal models, clinical trials, analyzing action potential side effects. The goal provide insights for future drug development applications. Moreover, challenges prospects multi-target combination therapies personalized medicine interventions practice offer strategic guidance comprehensive prevention management DCM.

Language: Английский

Citations

0